Verrucous carcinoma-an enigma: Case report and review.

Verrucous hyperplasia, verrucous keratosis, and VC may not be distinguished clinically or may coexist. Though it appears remarkably harmless, the histopathological diagnosis of VC should be accompanied with careful identification of tumors with a greater chance to become frank cancers. Here, we report two cases of OVC, referring all the diagnostic intricacy occurring in the clinicopathological examination along with a review of the scientific literature.

Introduction

Oral verrucous carcinoma (OVC) presents predominantly as an exophytic growth with a pebbly, micronodular surface, a slow growing rate and becomes locally invasive if not treated properly.[1] The first ever documented evidence of a Verrucous carcinoma dates back to 1941 when Fridell and Rosenthal reported a case of well-differentiated squamous cell carcinoma (SCC) of the oral cavity as “papillary verrucous carcinoma.”[2]

Verrucous carcinoma (VC) a variant of well-differentiated SCC was defined by Ackerman in 1948 as a diagnostically challenging squamous cell neoplasia involving lip, oropharyngeal, and laryngeal mucosa.[345] Various synonyms used to describe this tumor, including Ackerman's tumor, Buschke Lowenstein tumor, florid oral papillomatosis, epithelioma cuniculatum, and carcinoma cuniculatum.[5] The most common site of occurrence is oral cavity involving buccal mucosa, mandibular alveolar crest, gingiva, and tongue with glottic larynx being the most frequent nonoral site.[16]

Case Reports

Case 1

A patient aged 60 years came to the Department of OMR with a chief complaint of white growth in the right cheek region since 1 month. The growth was gradual in onset, and of the same size since the patient noticed it. No history of pain, bleeding, or difficulty in swallowing was reported. No history of any topical application and no similar growths were noticed elsewhere in the body. The right submandibular lymph nodes were palpable which were around 1 cm diameters soft and movable. Intraorally, a well-defined keratotic mass with finger-like projections on the surface was present of 4 cm × 5 cm, roughly oval in shape, well-defined borders extending from buccal mucosa of 47 to hard and soft palate faucial pillars, 3 cm in front of uvula anteroposteriorly and from 1 cm above line of occlusion on the right buccal mucosa up to the vestibule involving the retropharyngeal area, and lingual alveolar mucosa up to the alveololingual sulcus. On palpation, all inspectory findings are confirmed, nonscrapable, nontender, no bleeding on touch, and nonindurated [Figures 1 and 2]. A white keratotic patch was present on the right lateral border of the tongue of 2 cm × 3 cm, extending 1 cm from along the lateral border up to posterior aspect which was nontender and nonscrapable. Based on the clinical appearance provisional diagnosis of VC was given after which incisional biopsy taken confirmed the lesion as verrucous hyperplasia (VH).

Figure 1

Intraoral verrucous carcinoma of the right buccal mucosa in case 1

Figure 2

Verrucous carcinoma in case 1. Note the leukoplakia on the lateral border of tongue

Case 2

A second case wherein the patient aged 30 years came to our department with a chief complaint of growth in the retrocommissural area since 6 months. The growth was gradual in onset and was increasing in size since the patient noticed it. No history of pain, bleeding, or weight loss was reported. No history of any topical application and no similar growths were noticed elsewhere in the body. The left submandibular lymph nodes were palpable which were around 1.5 cm diameter, soft, and movable. Intraorally, two well-defined exophytic growths present with 3 cm × 4 cm in diameter each, with surface projections. The surrounding area is blanched and hypopigmented. On palpation, all inspectory findings were confirmed, and the lesion was nonscrapable, nontender, and nonindurated [Figures 3 and 4].

Figure 3

Intraoral lesion in case 2 on the left retrocommissural area

Figure 4

Intraoral lesion in case 2 with oral submucous fibrosis in the background

Palpable vertical bands were present in 36 and 26 regions. A provisional diagnosis of VC was given and after incisional biopsy, the diagnosis was as VH.

In the first case, the patient was habitual areca nut and tobacco chewer, and in the second case gutka chewer. Patient one had leukoplakia as other lesion, whereas patient two had oral submucous fibrosis.

A differential diagnosis of squamous papilloma, focal epithelial hyperplasia, VC, hypertrophic candidiasis, and condyloma acuminatum was put forward in both cases.

After excision, both cases were diagnosed as VC.

Discussion

Oral VC (OVC) is a slow growing lesion with exophytic growth pattern and predilection for males in fourth to sixth decade which becomes locally invasive if not treated properly.[12] Regional lymph node metastases are exceedingly rare, and distant metastases have not been reported.[34567] Enlarged lymph nodes often palpable are often reactive.[6] The findings in our cases were synchronous with these characteristics.

Betel nut chewing, poor dental hygiene, and human papillomavirus (HPV) infection have been implicated in the development of OVC.[347] The likelihood of detecting HPV in VC was found to be 29.5%.[7] Use of tobacco in the smokeless and inhaled forms has been predominantly reported in the affected patients, followed by areca nut chewing and use of alcohol.[8] In Ackerman's study, 11 out of 18 patients (61%) with buccal cancers were tobacco chewers.[6] Shear and Pindborg reported that out of 28 patients with verrucous lesions, 24 (86%) used tobacco and one was an areca quid chewer.[78] Tobacco appears to be a major factor in the causation of verrucous lesions.[8] In Chen et al.'s study of VCs in Taiwan, areca quid chewing has been reported by 97.3%.[8] Both the patients in our case had tobacco plus areca nut quid chewing habit which may have been the cause of the lesion.

Histomorphologic features include densely parakeratinized papillary surface, deep clefts in the epithelium, blunt and voluminous rete ridges with little or no dysplastic changes exhibiting a pushing border effect, and an intact basement membrane.[236] The resilient basement membrane probably acts as an effective barrier to prevent the carcinomatous growth.[1] VH has been considered as an early form of VC and is believed to have the same biological potential.[48] In hyperplasia, most of the hyperplastic broadened rete ridges lay above the adjacent normal epithelium while VC on contrary exhibits a downward growth pattern of otherwise similar rete ridges.[5] VC can also be mistaken as a benign lesion histologically.[34] In our case too, the first case was diagnosed as VH on incisional biopsy, whereas on a complete excision it was VC.

The clinico-histopathological diagnosis of VC is often exclusionary and extremely difficult.[4]

Because it is cytologically benign, besides the focal basal cell nuclear hyperchromatism, distinction from VC, and VH cannot be based only on cytologic features.

Multiple deep biopsies are recommended to avoid this problem.[7] VC should be analyzed regarding (a) conventional SCC, especially with those SCC showing “verrucoid” features, (b) proliferative verrucous leukoplakia, (c) reactive keratosis and epithelial hyperplasia, (d) pseudoepitheliomatous hyperplasia, (e) verruca vulgaris, and (f) keratoacanthoma according to the sites affected.[3457] A correct diagnosis is founded on the precise comparison and integration of all the results and not on the isolated valuation of the different findings. Nor should the VC be treated as lightly as VH nor should it be approached as invasive as SCC. Appropriate treatment is surgical excision. Using radiotherapy is controversial as there may be radiation-induced anaplastic transformation of the lesion as reported by some authors, whereas some suggest VC is radiosensitive.[34]

OVC associated with leukoplakia or submucous fibrosis may be an indication of “field cancerization” and can lead to multiple recurrences, so it is highly suggestive that such patients be kept under regular follow-up.[6] Our patients were on regular follow-up for a year, and no recurrence was reported.

Conclusion

The presence of malignant foci has been reported in OVC cases. Many times it is difficult for the oral diagnostician to differentiate clinically; hence, a thorough clinical knowledge and in-depth microscopic evaluation are required by both clinicians and pathologists to diagnose this dilemma. Thus, both clinicians and pathologists must be careful about warty and exophytic lesions in the oral cavity. We conclude that a correct diagnosis is based on the precise comparison and integration of all the results and not on the isolated valuation of the different findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.